The present invention relates to stinging cells capable of expressing an exogenous polynucleotide encoding a therapeutic, diagnostic or a cosmetic agent and to the use thereof or capsules derived therefrom in compositions, devices and methods for delivering the expressed therapeutic, diagnostic or cosmetic agent into a tissue.
Therapeutic proteinaceous agents, such as antibodies or peptide hormones are routinely used for the prevention, diagnosis, alleviation, treatment, or cure of diseases.
Biological, biochemical and/or physical barriers often limit delivery of such agents to target tissue. For example, skin and/or various organ membranes are physical barriers, which must be traversed by a topically administered agents targeted at internal tissues. Orally administered agents must be resistant to the low pH conditions and digestive enzymes present in the gastrointestinal (GI) tract.
To traverse such barriers, therapeutic agents targeted at internal tissues are often administered via a transdermal injection, using a syringe and a needle or other mechanical devices. A transdermal injection delivers such agents into the subcutaneous space thus traversing the epidermis-dermis layers.
Anatomically, the skin of a human body is subdivided into three compartments: an epidermis, a dermis and a subcutaneous layer, of which the epidermis plays a key role in blocking drug delivery via the skin (the dourest layer of the epidermis is the stratum corneum which is called also the horny layer). The epidermis is 0.1 mm or more in thickness and consists mainly of protein surrounded by lipid, thus rendering the epidermis hydrophobic.
Although the syringe and needle is an effective delivery device, it is sensitive to contamination, while use thereof is often accompanied by pain and/or bruising. In addition, the use of such a device is accompanied by risk of accidental needle injury to a health care provider.
Mechanical injection devices based on compressed gasses have been developed to overcome the above-mentioned limitations of syringe and needle devices. Such devices typically utilize compressed gas (such as, helium or carbon dioxide) to deliver medications at high velocity through a narrow aperture.
Although such devices traverse some of the limitations mentioned above, their efficiency is medication dependent, and their use can lead to pain, bruising and lacerations.
Other less common delivery methods utilize a pulsed Yag laser to perforate the stratum corneum in order to deliver agents via diffusion and enhancement of ionic compound flux across the skin by the application of an electric current. Although such methods are effective in delivering small charged molecules, a danger of skin burns accompanies their use.
Non-invasive methods, which overcome some of the limitations inherent to the invasive delivery methods described above, have also been described. Such methods utilize preparations, which include a therapeutic agent disposed within lipid vehicles (e.g., liposomes) or micelles or accompanied with skin permeation agent such that absorption of the active ingredient through the skin is enhanced. Such preparations can be directly applied to a skin region or delivered via transdermal devices such as membranes, pressure-sensitive adhesive matrices and skin patches.
In transdermal delivery, the active ingredient penetrates the skin and enters the capillary blood or the lymph circulation system, which carries the therapeutic agent to the target organ or to the tissue or has a local effect.
For several years, transdermal drug delivery systems have been employed to effectively introduce a limited number of drugs through unbroken skin. Aside from comfort and convenience, transdermal systems avoid the barriers, delivery rate control problems and potential toxicity concerns associated with traditional administration techniques, such as oral, intramuscular or intravenous delivery.
Although transdermal delivery offers an alternative to some invasive delivery methods, the efficiency thereof is affected by the physical and chemical properties of a drug and physiological or pathological parameters such as the skin hydration, temperature, location, injury, and the body metabolism.
In addition to delivery limitations, some proteinaceous drugs also suffer from limited stability making it difficult to store such drugs for extended time periods prior to use. A further limitation of conventional use of proteinaceous drugs is their limited solubility in many delivery vehicles, complicating dispersal and accurate dose delivery.
The present inventors propose a drug delivery approach utilizing stinging cells, (e.g. cnidocytes, nematocytes and the like) which express exogenous polynucleotides encoding a therapeutic, diagnostic or a cosmetic agent thereby traversing limitations associated with delivery and stability of expressed proteinaceous agents.